[Acute pancreatitis and propylthiouracil].
Explore the source record for details and available documents.
Acute Disease↗
Biomedical subjects
C Even
Publications and source records attributed to C Even.
Neonatal infection of mice with lactate dehydrogenase-elevating virus results in suppression of humoral antiviral immune response but does not alter the course of viraemia or the polyclonal activation of B cells and immune complex formation.
Neonatal infection of FVB mice with lactate dehydrogenase-elevating virus (LDV) prevented the normal formation of anti-LDV antibodies observed in mice infected at 5 days of age or older. Even 22 weeks post-infection, the concentration of circulating anti-LDV antibodies in neonatally infected mice was insignificant. However, the time course and level of persistent viraemia were the same in neonatally infected mice lacking anti-LDV antibodies as in mice infected at 5 or 15 days of age which developed normal antiviral immune responses. The results support the view that LDV replication in mice is unaffected by antiviral immune responses and instead is primarily dependent on the rate of regeneration of LDV-permissive macrophages. This view is further supported by the following findings. Treatment of mice with cyclophosphamide or dexamethasone, which are known to increase plasma LDV levels, increased the proportion of LDV-permissive macrophages in the peritoneum. Injection of mice with interleukin-3, which is known to stimulate macrophage development, increased plasma LDV levels in persistently infected mice 10- to 100-fold. During the first month of age when mice possess a higher proportion of LDV-permissive macrophages than older mice and peritoneal macrophages exhibit self-sustained growth, the persistent plasma LDV titres were also 10- to 100-fold higher than in older mice. The polyclonal activation of B cells induced by LDV that results in a permanent elevation of IgG2a or IgG2b in the circulation, and the formation of 180K to 300K immune complexes containing IgG2a or IgG2b were also the same in neonatally infected mice and mice infected 5 or 15 days after birth. Thus, the polyclonal activation of B cells occurs in the absence of an antiviral humoral immune response and the immune complexes do not contain anti-LDV antibodies. The immune complexes probably consist of autoantibodies formed in the course of the polyclonal activation of B cells and their cellular antigens.
Animals↗
Sequences of 3' end of genome and of 5' end of open reading frame 1a of lactate dehydrogenase-elevating virus and common junction motifs between 5' leader and bodies of seven subgenomic mRNAs.
The sequences of the 3'-terminal 3.7 kb of the genome and of a 1.7 kb 5' end cDNA clone of one isolate of lactate dehydrogenase-elevating virus (LDV) are reported. The 3' end sequence encodes six major independent open reading frames (ORFs 2 to 7), which are overlapping by between one and 130 nucleotides. Each ORF is expressed at the 5' end of one of six 3'-coterminal subgenomic mRNAs (mRNAs 2 to 7, respectively; 3.5 to 0.8 kb). The smallest mRNA, mRNA 7, encodes the nucleocapsid protein, VP1; mRNA 6 probably encodes the non-glycosylated envelope protein, VP2; and mRNAs 2 to 5 encode proteins of 26.0K, 21.5K, 19.2K and 22.4K, respectively, each possessing several potential N-glycosylation sites and membrane-spanning segments. About 72% of the LDV genome segment carrying ORFs 2 to 7 exhibits about 50% or higher nucleotide identity with the corresponding genome segment of swine infertility and respiratory syndrome (Lelystad) virus (LV), whereas only limited similarity is observed in discontinuous regions of the same corresponding genome segments of LDV and equine arteritis virus (EAV). EAV and LV belong to the same new group of positive-strand RNA viruses as LDV. One additional subgenomic mRNA of about 4 kb is produced in LDV- but not in EAV- or LV-infected cells. The 5' end of this mRNA (1-1) carries a continuous coding sequence. The N-terminal 80 amino acids of the predicted product exhibit about 50% identity with segments in the ORF 1b proteins of both EAV and LV. These segments are located 117 to 150 amino acids upstream of the C termini of the ORF 1b proteins of these viruses. The 5' end cDNA clone contains part of a 5' leader associated with all seven subgenomic mRNAs and the 5' end of ORF 1a. The junctions between the 5' leader and the bodies of all seven subgenomic mRNAs have been determined. Only a single junction sequence was detected for each mRNA. Linkage occurs between a 5' UAUAACC 3' sequence at the 3' end of the leader and only partially identical segments specified downstream in the genome preceding ORFs 2 to 7. The generated junctions differ for different subgenomic mRNAs but possess the consensus sequence 5' U(A/G)(U/A)AACC 3'. In mRNA 7, the UA in positions 1 and 2 are derived from the leader, but a G in position 2 in mRNAs 1-1, 3 and 4 and an A in position 3 in mRNA 6 seem to be specified by the 3' genomic sequences.(ABSTRACT TRUNCATED AT 400 WORDS)
Amino Acid Sequence↗
Mode of neutralization of lactate dehydrogenase-elevating virus by polyclonal and monoclonal antibodies.
Neutralization of the infectivity of [3H]uridine-labeled lactate dehydrogenase-elevating virus (LDV) by polyclonal mouse or rabbit antibodies to the envelope glycoprotein of LDV, VP-3, or by neutralizing monoclonal antibodies (mAb) that recognize a different epitope on VP-3 than the polyclonal antibodies correlated with an increase in the sedimentation rate of LDV from 230 S to greater than or equal to 270 S. Incubation of LDV with normal mouse plasma or non-neutralizing mAbs to LDV VP-3 had no effect on its sedimentation rate. Similarly, incubation of a neutralization escape variant of LDV with the mAb used in its selection had no effect on its sedimentation rate, whereas neutralization of this variant by polyclonal mouse or rabbit anti-VP3 antibodies increased the sedimentation rate. Neutralization of LDV infectivity was only observed at high antibody/virion ratios and often was followed by loss of the viral RNA. The results suggest that neutralization of LDV infectivity results from binding of multiple antibody molecules that recognize specific epitopes on the viral envelope glycoprotein and ultimately leads to disintegration of the virions.
Animals↗
Immune complexes that bind to ELISA plates not coated with antigen in mice infected with lactate dehydrogenase-elevating virus: relationship to IgG2a- and IgG2b-specific polyclonal activation of B cells.
We have further investigated the nature of IgG-containing complexes of 150-300 kD that rapidly appear in the circulation of mice of various strains after infection with lactate dehydrogenase-elevating virus (LDV) and are recognized and quantitated by their binding in the presence of 0.05% Tween 20 to certain enzyme-linked immunosorbent assay (ELISA) plates with high protein affinity that have not been coated with protein antigen (5). These binding complexes have been found to contain primarily IgG2a or, in some mice, IgG2b. Their isotype specificity and time course of formation correlated with those of the polyclonal production of immunoglobulins in these mice, as measured by increases in total IgG2a or IgG2b in the circulation. In contrast, anti-LDV antibodies exhibited much broader isotype specificities in all mouse strains investigated. Depletion of BALB/c mice of CD4+T cells or lack of T cells in nude Swiss mice only partly reduced the polyclonal activation of B cells and the formation of ELISA plate-binding complexes, whereas anti-LDV antibody formation was completely blocked. Only a small proportion of the total IgG2a or IgG2b formed as a result of the LDV-induced polyclonal activation of B cells was recovered in plate-binding complexes, which sedimented in sucrose density gradients between 150 and 300 kD. Diverse monoclonal antibodies of different IgG isotopes did not bind to the plates at concentrations at which LDV-induced immune complexes exhibited binding activity. We suggest that the LDV-induced immune complexes do not contain anti-LDV antibodies, but are complexes of auto-antibodies and self-antigen(s). However, additional features must be responsible for the high affinity of these complexes for ELISA plates since various immune complexes formed in vitro failed to bind to the plates, and binding activity of the immune complexes formed in LDV-infected mice could not be regenerated in vitro once the complexes had been dissociated by a low pH treatment.
Animals↗
Correlation between levels of immunoglobulins and immune complexes in plasma of C57BL/6 and C57L/J mice infected with MAIDS retrovirus.
Infection with helper-free, defective MAIDS murine leukemia virus (MuLV) caused a rapid polyclonal activation of B cells in 0.75-, 2-, and 6-month-old C57L/J mice (H-2b, Fv-1n/n), similar to that in C57BL/6 mice (H-2b, Fv-1b/b), which was recognized by elevated plasma immunoglobulin concentrations. However, changes in plasma immunoglobulin levels differed in C57BL/J and C57BL/6 mice. In C57L/J mice, infection resulted in a rapid increase in plasma IgM and IgG2a, and the elevation of IgG2a persisted undiminished for 21 weeks. Levels of IgG2b also became slightly elevated, but those of IgG1 and IgG3 were not significantly affected. Plasma of 6 to 7-month-old C57BL/6 mice contained already high levels of IgM (30-40 mg/ml), which persisted undiminished in uninfected mice but decreased progressively in infected mice to 10% of the original concentration during 25 weeks of observation. In C57BL/6 mice, plasma IgG1 and IgG2b as well as IgG2a became similarly elevated after infection but also only transiently. Their levels began to decrease progressively about 10 weeks after infection and fell to far below the maximum concentration observed. The drastic loss of plasma IgM and IgGs observed in C57BL/6 mice during the later stages of MAIDS MuLV infection did not seem to be a consequence of the polyclonal activation of B cells per se but seemed to reflect additional immunological abnormalities arising in infected C57BL/6 but not C57L/J mice. In both mouse strains these changes in plasma Ig levels correlated with the formation of Ig-containing immune complexes that bound to high-affinity, protein-binding ELISA plates in the absence of antigen coating, which may represent unusual forms of self-antigen-antibody complexes.
Animals↗
Polyclonal B cell activation of IgG2a and IgG2b production by infection of mice with lactate dehydrogenase-elevating virus is partly dependent on CD4+ lymphocytes.
Concentrations of IgM and IgG isotypes were determined by capture ELISA in plasma of Swiss, BALB/c and C58/M mice. Plasma IgG isotype concentrations, especially of IgM, IgG1 and IgG2a, varied considerably between mouse strains, batches of mice of the same strain and individual mice and as a function of age. Infection of the mice with LDV, which is known to replicate primarily in a subpopulation of macrophages, consistently resulted in a rapid elevation of plasma IgG2a (or of IgG2b in some Swiss nu/+ mice), but no plasma IgG increases were observed in mice immunized with inactivated LDV. Plasma IgG2a elevation after LDV infection was greatly delayed and reduced by depletion of the mice of CD4+, but not of CD8+, T cells by administration of protein-G-purified anti-CD4 or anti-CD8 mAbs, and completely inhibited by repeated treatment of the mice with cyclophosphamide. Treatment with anti-CD4 mAbs, or cyclophosphamide also greatly reduced the production of anti-LDV antibodies, while not significantly affecting the replication of LDV in these mice. Nude Swiss mice also failed to produce anti-LDV antibodies, though supporting normal LDV replication. Plasma IgM, IgG1, IgG2a and IgG2b levels increased in LDV-infected nu/nu mice, but similar changes were observed in uninfected mice. The results indicate that the LDV-induced polyclonal activation of B cells requires productive LDV infection of mice and is, at least partly, dependent on functioning CD4+ cells. They suggest that productive infection of the LDV-permissive subpopulation of macrophages leads to the activation of CD4+ T lymphocytes of subset 1 and their Spleen cells from 5-day LDV-infected BALB/c mice incorporated [3H]thymidine 2-3 times more rapidly in vitro than spleen cells from companion uninfected mice, whereas their responses to concanavalin A and lipopolysaccharide were reduced 60-70%.
Animals↗
Persistent infection of mice by lactate dehydrogenase-elevating virus: effects of immunosuppression on virus replication and antiviral immune responses.
Maximum plasma titers (10(9)-10(10) ID50/ml) of lactate dehydrogenase-elevating virus (LDV) in mice are observed one day after infection, but then decrease 4-5 log during the next 5 weeks to attain a persistent steady-state level for the remainder of the life of the animal. The decrease in plasma LDV level during the first 5 weeks after infection and long-term viremia were not affected by lethal X-irradiation of the mice, daily injections of cyclosporin A or depletion of the mice of T cells by treatment with anti-CD4, anti-CD8, or anti-Thy1.2 monoclonal antibodies, although these treatments inhibited the formation of anti-LDV antibodies. LDV viremia was also the same in nu/nu and nu/+ Swiss mice, though the former did not mount an anti-LDV immune response, while the latter did. The appearance of anti-LDV neutralizing antibodies in infected mice 1-2 months after infection or the injection of infected mice with high doses of anti-LDV neutralizing monoclonal antibodies also did not affect the level of LDV viremia. Repeated treatments of infected mice with either cyclophosphamide or dexamethasone caused 1-2 log increases in plasma LDV titers. Although cyclophosphamide treatment prevented the formation of anti-LDV antibodies, dexamethasone caused an increase in plasma LDV levels without affecting anti-LDV antibody formation. We conclude that an anti-LDV immune response does not play a significant role in controlling LDV replication in mice. The data support the view that within 1 day after infection of a mouse, all LDV-permissive macrophages, which appear to be the only cells supporting LDV replication in the mouse, are destroyed as a result of a cytocidal infection by LDV. Subsequently, LDV replication is limited by the rate of generation of new permissive macrophages. The steady-state viremia attained about 5 weeks after infection reflects a balance between LDV replication in permissive macrophages as they arise and LDV inactivation and clearance.
Animals↗
[Mixed states in bipolar disorders: a review of current therapeutic strategies].
Mixed states are characterized by the mixture or rapid alternation, within hours, of manic and depressive symptoms. They bear a high suicidal risk and therefore represent a major therapeutic issue. We performed a computerized bibliographic search and reviewed the efficacy of the available treatments of mixed states. It confirmed the recognized poor efficacy of lithium and the need to discontinue antidepressants. Among mood stabilizers, divalproate and its derivatives are those with the highest level of evidence. As regards new anticonvulsants, the data are yet too limited to recommend them as first line treatments. They may however be used as second line or adjunct treatments in case a monotherapy with a reference treatment has failed. Among antipsychotic drugs, clozapine has demonstrated its efficacy but also remains a second line treatment due to its high risk of neutropenia and agranulocytosis. Electroconvulsive therapy is a useful alternative in treatment resistant cases or when there is an imminent risk for suicide. Some degree of uncertainty remains for the treatment of the so called "agitated depressions" as no study has yet focused on this issue with a specifically selected sample of patients. Such a study would also enlighten the uncertain nosological status of this clinical entity and would answer as to whether they belong to the category of mixed states.
Antidepressive Agents↗
[Pregnancy, breast feeding and mood stabilisers: review and recommendations for practice].
INTRODUCTION: The high prevalence of bipolar affective disorder, the early age of onset and the even sex ratio imply that numerous women of childbearing age raise the question of mood stabilisers during pregnancy and breast feeding. LITERATURE FINDINGS: Some data suggest that giving appropriate answers to bipolar women who want to have children is an unmet need. We reviewed the risks and therapeutic options of this period of life in women with bipolar disorder. The generally accepted idea that pregnancy protects from relapses in bipolar disorders may be untrue and even deceitful. Lithium is the only mood stabiliser that can be prescribed in some cases during the first three months of pregnancy. DISCUSSION AND GUIDE LINES: We give explicit criteria that allow to consider this option: a severe illness prior to lithium prescription, a highly favourable outcome since initiation of lithium, no relapse during the last 18 months. When such conditions are satisfied, a reflection of the patient and at best of the couple must be proposed and associated with very complete information, both oral and written when possible, on the risks and benefits of the interruption and/or continuation of lithium. The teratogenic risks with anticonvulsants have been demonstrated and their prescription during the first three months of pregnancy should be avoided. Besides, there is some concern about the psycho-motor development of children born from women who were under anticonvulsants during pregnancy. The more recent mood stabilisers are not recommended either due to insufficient data. Breast feeding is not recommended under lithium, but seems safe under carbamazepine or valproate and its derivatives.
Anticonvulsants↗
[determining factors of depression in multiple sclerosis: review of the literature].
Depression is considered to occur more frequently in multiple sclerosis than in other chronic organic disorders. The determining factors of this specific association have been appraised by most authors in a dichotomic manner, confronting organic to psychogenic hypotheses. To assess these hypotheses two investigational methods have been used in the literature: either the search for correlations between depression and other parameters linked to the neurologic process, or the comparison of the course of neurologic and thymic symptoms. Systematically scrutinizing this literature enabled us to discuss its findings as well as its methodologic and conceptual limitations.
Cognition Disorders↗
[Actual approaches to post-psychotic depression].
Clinical features of post-psychotic depression in schizophrenia have been described since the beginning of the century. However, international nosographies mention this concept only since the ICD 10 and the DSM IV. In clinical practice, post-psychotic depression is a real challenge. Currently, the exact prevalence remains undetermined and is estimated about 25%, varying from 7 to 70% in the literature. The diagnostic criteria nowadays available will encourage searchers to determine the exact prevalence of post-psychotic depression. This is surely due to difficulties in the diagnostic approach. The clinical picture resembles that of major depression. However, there are confounding factors such as negative symptoms and extrapyramidal symptoms. With regard to psychometrics, two specific rating scales are thought to measure depressive symptoms in schizophrenia: the Calgary Depression Scale (CDS) and the Psychotic Depression Scale (PDS). Nonetheless, the scales are not specific for post-psychotic depression. Prognosis of an acute schizophrenia is linked among other factors with the emergence of a post-psychotic depression that is in turn influences suicidal risk and quality of life. Genetic, therapeutic, psychodynamic and psychological factors have been invoked in the etiopathogenesis of post-psychotic depression. In clinical practice, post-psychotic depression can be successfully treated with antidepressive medication. Some antidepressants have shown their efficacy.
Acute Disease↗
[Tricyclic antidepressants dosage and depressed elderly inpatients: a retrospective pharmaco-epidemiologic study].
UNLABELLED: It is recommended to reduce by one half the dosages of tricyclic antidepressants for patients over 65 years of age, in order to avert the occurrence of side-effects. The question we studied was: is it rightful to prescribe tricyclic antidepressants at half-dose to hospitalized elderly people? It is important, for the following reasons, to specify the rules of prescription of tricyclics in elderly patients: 1) The elderly population is on the increase; 2) There is a high prevalence of depression in elderly patients; 3) Depression exposes the elderly person to an increased risk of suicide; 4) Depression influences the prognosis of associated organic disorders 5) Recourse to tricyclic antidepressants is often necessary within this population group because of treatment resistant forms of depression which impose the use of different families of antidepressants and thus resort to tricyclics despite their lower tolerance. OBJECTIVES AND METHODS: The aim of our study is to evaluate whether the half doses of tricyclics recommended for an elderly person are sufficient in the case of an hospitalized patient. In order to provide some answer to this question, we have carried out a retrospective study. We have studied a sample of patients over-65, hospitalized at the Clinique des Maladies Mentales et de l'Encéphale, over a period of two years, with a ICD 10 diagnosis of moderate or severe intensity major depressive episode, and treated effectively with return to the euthymia. Creatinemia was prescribed systematically to each patient on entry. Only patients with normal renal function were retained. Laboratory norms are between 45 and 120 micromol/liter. The routine practice of imipraminic blood dosages allowed the comparison of blood levels obtained among patients treated with posologies inferior or equal to 75 mg/day imipraminic, to those treated with more than 75 mg/day imipraminic for a least a week. The percentage observed were compared using the Khi2 test with Yates correction. We retained the blood concentrations of the mother molecule for tertiary amines (imipramine, clomipramine and amitriptyline). The samples were taken after at least seven days of treatment at the same dose, and twelve to thirteen hours after the last taking. The maxima of blood levels were respectively: desipramine 200 ng/ml, clomipramine 258 ng/ml, imipramine 163 ng/ml, amitriptyline 129 ng/ml. Research for evidence in favor of toxicity (fall, delirium, convulsion, reduction of dosage before discharge), was done through revision of patients' clinical files. RESULTS: The test group consisted of 87 individuals. The average age was 71.3 years (SD: 5.09). Mean creatinemia was 83.73 mmol/l (SD: 26.89). The population thus selected divided into 4 groups: 61 (70.1%) were given imipraminics, 10 (11.5%) serotonin recapture inhibitors, 11 (12.7%) other antidepressants essentially of mianserine and 5 (5.7%) treatment by electroconvulsivotherapy. The imipraminics prescribed were desipramine, imipramine, clomipramine and amitriptyline. Among the 61 patients treated with imipramine, blood level dosage was practised on 48 patients (79%). Two subgroup were distinguished: 13 (21%) received dosages inferior ou equal to 75 mg/day and 48 (79%) superior to 75 mg/day. The mean dosage found in the sub-group of patients treated with dosages superior to 75 mg/day was 140 mg/day (SD: 30). The subgroup treated with dosages superior to 75 mg/day was more frequently monitored than the subgroup receiving dosages inferior or equal to 75 mg/day, respectively 40/48 (83%), and 8/13 (62%). This difference is statistically nonsignificant (p > 0.10). The analysis of dosages used showed that:--among the dosages effected upon patients receiving doses inferior or equal to 75 mg/day, 1 (12.5%) exceeded the maximal value of therapeutic range.--Among the dosages effected upon patients receiving dosages superior to 75 mg/day, 9 (22%) exceeded the maximal value of the therapeutic range. The difference is statistically significant (p < 0.001). On revision of clinical files, no patient presented any element that might lead one to suspect toxicity such as defined in "Objectives and Methods". CONCLUSION: In our study, patients were hospitalized and so benefited from closer observation than one can expect in outpatients. In this particular context, the dosages used are close to those advocated for the general population. With the elderly subject, the systematic prescription of half-dose tricyclics runs the risk of infratherapeutic dosage. It is thus preferable to resort to blood level dosage and to look for a maximum dose tolerance before concluding ineffectuality. This allows one to monitor whether the blood levels obtained are included in the therapeutic range; to avoid toxic doses and to check weak compliance in the elderly patient. Our findings do not oppose the use, for the elderly hospitalized depressive, of doses of imipraminics close to those of a young subject. To confirm these results it would be desirable to carry out o prospective study, including a systematised evaluation of adverse effects and a comparison of clinical effectiveness for parallel groups of elderly patients receiving different doses of imipraminic antidepressants.
Aged↗
[Bipolar I disorder in France: prevalence of manic episodes and hospitalisation-related costs].
Bipolar disorder is a chronic, highly disabling illness. However, few studies have evaluated the economic impact of this illness. The objective of this study was to estimate: 1) the annual number of manic episodes in patients with bipolar I disorder, and 2) the costs of hospitalisations related to manic episodes in France. We only included data on bipolar I disorder, as there is greater consensus and better documentation for this subgroup of patients with bipolar disorder. The prevalence of manic episodes was estimated using published epidemiological data. A computerised literature search was performed using the traditional scientific and medical databases. Additional epidemiological references were identified from published studies and textbooks. For hospitalisation data, we used the statistics of the Medical Information Department of a large psychiatric hospital in Paris for the year 1999. We estimated the annual number of manic episodes in France based on: 1) the lifetime prevalence of bipolar I disorder, 2) the average cycle duration, 3) the proportion of rapid cycling patients, and 4) the proportion of depressive vs. manic episodes for patients with bipolar I disorder. In order to estimate the prevalence of bipolar I disorder, we conducted a random effects meta-analysis using published international data. Results of the meta-analysis, which was based on a total of 62 736 patients, showed the lifetime prevalence of bipolar I disorder to be 0.82% [95% CI: 0.42, 1.21]. Applied to the adult population in France, this prevalence implies that the number of persons who have ever experienced a bipolar I -disorder is approximately 390,000 [95% CI: 200,000, 575,000]. Few studies provide information on the duration of cycles in patients with bipolar I disorder. Available estimates suggest the cycle duration to be approximately 12 months. Regarding the proportion of rapid cyclers, data from the meta-analysis by Tondo et al. show that 18% of patients with bipolar disorder experience at least four episodes of mood disorder per year. Finally, based on findings provided by cohort studies, the number of depressive episodes appears to be roughly equal to the number of manic episodes during the course of bipolar disorder. A rapid cycling rate of 18% and a cycle duration of 12 months imply that, on average, among 100 bipolar patients, 18 will have a 3-month cycle duration and 82 a 14-month cycle duration. Given an equal proportion of manic and depressive episodes, the annual number of manic episodes would then be 68 for a cohort of 100 bipolar patients (0.68 episode per patient per year). Applying this figure to the estimate of the total number of patients with bipolar I disorder in France suggests that the annual number of manic episodes in France is 265,000 [95% CI: 136,000, 391,000]. Based on data from a psychiatric hospital in Paris, the proportion of manic episodes that require hospitalisation was estimated to be around 63% with an average length of stay of 32.4 days. Hence the annual number of hospitalisations for manic episodes in France is estimated to be 167 000 [95% CI: 86 000, 246 000] and the hospitalisation-related costs 1,3 billion euros approximately. Our review of literature highlights the lack of medical and economic data at the national level on the frequency and hospitalisation-related costs of manic episodes in patients with bipolar I disorder in France. Given the lifetime prevalence of bipolar I disorder which may be as high as 3% among adults, further studies are required in order to provide representative national data and to allow economic evaluations of costs related to bipolar disorder in France.
Adolescent↗
[Central serotonin receptors and chronic treatment with selective serotonin reuptake inhibitors in the rat: comparative effects of fluoxetine and paroxetine].
The hypothesis that a dysfunction of serotonergic neurotransmission is implicated in depression is supported by the clinical efficiency of selective serotonin (5-hydroxytryptamine, 5-HT) reuptake inhibitors (SSRIs) in the treatment of depressive disorders. These drugs, such as fluoxetine and paroxetine, exert their antidepressant activity by increasing 5-HT concentration in the synaptic cleft and thus enhancing serotonergic neurotransmission. However, two to three weeks of treatment are necessary to see the first signs of clinical efficiency. Several hypothetical mechanisms have been put forward to account for this delay, taking into account pharmacokinetic considerations, neurotransmitter metabolism, and/or adaptive regulation of pre and/or post-synaptic receptors. The aim of this study was to look for such adaptive changes in the course of a 3-week treatment with fluoxetine (5 mg/kg/day, i.p.) or paroxetine (5 mg/kg/day, i.p.) in adult rats. In vitro binding and quantitative autoradiographic studies showed that neither 5-HT1A, 5-HT1B, 5-HT2A, nor 5-HT3 receptor binding sites in various brain areas were affected by these treatments. Furthermore, comparison of the specific binding of [3H]8-OH-DPAT to 5-HT1A receptors functionally coupled to G proteins with that of [3H]WAY 100635 to all 5-HT1A receptor binding sites (i.e. coupled and uncoupled with regard to G proteins) revealed no significant change in rats treated with either SSRI. Accordingly, the proportion of functional 5-HT1A receptors (i.e. those physically coupled to G proteins) appeared to remain unaltered all along a 3-week treatment with either fluoxetine or paroxetine. Nevertheless, in vitro electrophysiological recordings of serotonergic neurons in the dorsal raphe nucleus allowed the demonstration of a clearcut functional desensitization of somatodendritic 5-HT1A autoreceptors. Thus, the potency of the 5-HT1A autoreceptor agonist, 8-OH-DPAT, to depress the firing of serotonergic neurons in brain stem slices was significantly reduced as soon as after a 3-day treatment with either SSRI. The proportion of recorded neurons showing desensitization of somatodendritic 5-HT1A autoreceptors then increased along the treatment, and was generally larger with fluoxetine than with paroxetine. As 5-HT1A autoreceptor desensitization can contribute to facilitate serotoninergic neurotransmission, the remarkable efficiency of fluoxetine to trigger this adaptive regulatory mechanism might account, at least partly, for its potent antidepressant activity.
Animals↗
[Bipolar affective disorder and Ekbom syndrome: apropos of a case].
A delusion of parasitosis may be seen in patients with a variety of organic and psychiatric disorders. It may also be a primary delusion often referred to as the "Ekbom syndrome". The nosological categorization of this rare condition is still under debate. We report the case of a 81 year-old woman followed in our department during more than 20 years for a bipolar affective disorder. Five years ago she developed a persistent delusion of parasitosis displaying phenomenological characteristics that are typical of the Ekbom syndrome. Given the complete independence of the respective courses of affective and delusional symptoms, we concluded in favour of a genuine comorbid association between two independent disorders. To our knowledge this association has not heretofore been described in the French or English language literature. It raises questions regarding the connections between affective disorders and delusions of parasitoris.
Aged↗